22-24495397-C-G
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_016327.3(UPB1):c.-7C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,612,786 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 5 hom. )
Consequence
UPB1
NM_016327.3 5_prime_UTR
NM_016327.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.48
Genes affected
UPB1 (HGNC:16297): (beta-ureidopropionase 1) This gene encodes a protein that belongs to the CN hydrolase family. Beta-ureidopropionase catalyzes the last step in the pyrimidine degradation pathway. The pyrimidine bases uracil and thymine are degraded via the consecutive action of dihydropyrimidine dehydrogenase (DHPDH), dihydropyrimidinase (DHP) and beta-ureidopropionase (UP) to beta-alanine and beta-aminoisobutyric acid, respectively. UP deficiencies are associated with N-carbamyl-beta-amino aciduria and may lead to abnormalities in neurological activity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 22-24495397-C-G is Benign according to our data. Variant chr22-24495397-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 340927.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UPB1 | NM_016327.3 | c.-7C>G | 5_prime_UTR_variant | 1/10 | ENST00000326010.10 | NP_057411.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UPB1 | ENST00000326010.10 | c.-7C>G | 5_prime_UTR_variant | 1/10 | 1 | NM_016327.3 | ENSP00000324343 | P1 | ||
UPB1 | ENST00000382760.2 | c.-7C>G | 5_prime_UTR_variant | 1/4 | 5 | ENSP00000372208 | ||||
UPB1 | ENST00000415388.5 | c.-7C>G | 5_prime_UTR_variant, NMD_transcript_variant | 1/9 | 5 | ENSP00000400684 |
Frequencies
GnomAD3 genomes AF: 0.00152 AC: 231AN: 152236Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00156 AC: 388AN: 249428Hom.: 2 AF XY: 0.00157 AC XY: 212AN XY: 135064
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GnomAD4 exome AF: 0.00212 AC: 3092AN: 1460432Hom.: 5 Cov.: 33 AF XY: 0.00209 AC XY: 1516AN XY: 726610
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GnomAD4 genome AF: 0.00152 AC: 231AN: 152354Hom.: 2 Cov.: 32 AF XY: 0.00134 AC XY: 100AN XY: 74498
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deficiency of beta-ureidopropionase Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at